Unguided low intensity cognitive behaviour therapy for anxiety and depression during the COVID-19 pandemic: A randomised trial.

The COVID-19 pandemic has had a severe impact on mental health worldwide, with increased rates of anxiety and depression widely documented. The aim of this study was to examine unguided low intensity cognitive behaviour therapy for anxiety and depression during the pandemic. A sample of 225 individuals in Australia and the United Kingdom (M age 37.79, SD = 14.02, range 18-80 years; 85% female) were randomised into intervention or waitlist control. The intervention group demonstrated significant decreases in anxiety (d = 0.36 [0.18, 0.54]) and depression (d = 0.28 [0.11, 0.45]) compared to controls. The majority of participants (96%) rated the intervention as useful, and most (83%) reported they spent 30 min or less reading the guide, with 83% agreeing the intervention was easy to read. The results indicate that low intensity cognitive behaviour therapy has efficacy in reducing anxiety and depression during the COVID-19 pandemic. There is an urgent need to disseminate low intensity psychological therapies to improve mental health in this challenging time

Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively

Unusual 1,6-diphenyl-1,3,5-hexatriene (DPH) spectrophotometric behavior in water/ethanol and water/DMSO mixtures

The absorption spectra of DPH at fixed concentration do not change with water content in organic solvents. It exhibits monomer bands, such as those obtained in ethanol. The absorption did not change for solutions up to 54 and 46% of water in ethanol and DMSO, respectively, for [DPH] = 5.0 × 10-6 mol L-1 at 30 °C. However, at the same experimental conditions, a gradual sharp decay of the DPH fluorescence is observed. It is proposed that water molecules below these water concentration limits act as quenchers of the excited states of DPH. Stern-Volmer quenching constants by intensities measurements are 7.4 × 10-2 (water/ethanol) and 2.6 × 10-2 L mol-1 (water/DMSO). DPH lifetime measurements in the absence and presence of water resulted in 7.1 × 10-2 L mol-1 in water/ethanol, which pointed out that the process is a dynamic quenching by water molecules. For experiments using DPH as probe, this process can affect data, leading to misunderstanding interpretation.O espectro de absorção de DPH, em concentração fixa, não varia com o teor de água em solvente orgânico. Tem-se a banda de monômeros igual àquela em etanol puro. A absorção não muda até o limite de 54 e 46% de água em etanol e DMSO, respectivamente, para [DPH] = 5,0 × 10-6 mol L-1 a 30 °C. Entretanto, em misturas com água muito abaixo desses conteúdos críticos, observou-se um decaimento intenso de fluorescência enquanto a absorção manteve-se constante. Propõe-se que moléculas de água atuam como supressores dos estados excitados e a constante de supressão de Stern-Volmer através de intensidade relativas, resultou em 7,4 × 10-2 (água/etanol) e 2,6 × 10-2 L mol-1 (água/DMSO). Os tempos de vida do DPH na ausência e presença do supressor forneceram constantes de 7,1 × 10-2 L mol-1 em água/etanol, indicando supressão dinâmica. Em investigações de ambientes com esta sonda, este processo deve ser considerado tendo em vista o risco de erros de interpretação

Photoelectrochemical H2 Evolution with a Hydrogenase Immobilized on a TiO2-Protected Silicon Electrode.

The combination of enzymes with semiconductors enables the photoelectrochemical characterization of electron-transfer processes at highly active and well-defined catalytic sites on a light-harvesting electrode surface. Herein, we report the integration of a hydrogenase on a TiO2-coated p-Si photocathode for the photo-reduction of protons to H2. The immobilized hydrogenase exhibits activity on Si attributable to a bifunctional TiO2 layer, which protects the Si electrode from oxidation and acts as a biocompatible support layer for the productive adsorption of the enzyme. The p-Si|TiO2|hydrogenase photocathode displays visible-light driven production of H2 at an energy-storing, positive electrochemical potential and an essentially quantitative faradaic efficiency. We have thus established a widely applicable platform to wire redox enzymes in an active configuration on a p-type semiconductor photocathode through the engineering of the enzyme-materials interface

Effects of partner proteins on BCA2 RING ligase activity

Abstract Background BCA2 is an E3 ligase linked with hormone responsive breast cancers. We have demonstrated previously that the RING E3 ligase BCA2 has autoubiquitination activity and is a very unstable protein. Previously, only Rab7, tetherin, ubiquitin and UBC9 were known to directly interact with BCA2. Methods Here, additional BCA2 binding proteins were found using yeast two-hybrid and bacterial-II-hybrid screening techniques with Human breast and HeLa cDNA libraries. Co-expression of these proteins was analyzed through IHC of TMAs. Investigation of the molecular interactions and effects were examined through a series of in vivo and in vitro assays. Results Ten unique BCA2 interacting proteins were identified, two of which were hHR23a and 14-3-3sigma. Both hHR23a and 14-3-3sigma are co-expressed with BCA2 in breast cancer cell lines and patient breast tumors (n = 105). hHR23a and BCA2 expression was significantly correlated (P = \u3c 0.0001 and P = 0.0113) in both nucleus and cytoplasm. BCA2 expression showed a statistically significant correlation with tumor grade. High cytoplasmic hHR23a trended towards negative nodal status. Binding to BCA2 by hHR23a and 14-3-3sigma was confirmed in vitro using tagged partner proteins and BCA2. hHR23a and 14-3-3sigma effect the autoubiquitination and auto-degradation activity of BCA2. Ubiquitination of hHR23a-bound BCA2 was found to be dramatically lower than that of free BCA2, suggesting that hHR23a promotes the stabilization of BCA2 by inactivating its autoubiquitination activity, without degradation of hHR23a. On the other hand, phosphorylated BCA2 protein is stabilized by interaction with 14-3-3sigma both with and without proteasome inhibitor MG-132 suggesting that BCA2 is regulated by multiple degradation pathways. Conclusions The interaction between BCA2 and hHR23a in breast cancer cells stabilizes BCA2. High expression of BCA2 is correlated with grade in breast cancer, suggesting regulation of this E3 ligase is important to cancer progression

Selection of antigenically advanced variants of seasonal influenza viruses

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent se

Selection of antigenically advanced variants of seasonal influenza viruses.

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014-2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.This work was supported by the Bill & Melinda Gates Foundation Global Health Grant OPPGH5383; National Institute of Allergy and Infectious Diseases (NIAID) Public Health Service research grants (USA); ERATO (Japan Science and Technology Agency); the Center for Research on Influenza Pathogenesis (CRIP) funded by the NIAID Contracts HHSN266200700010C and HHSN27 2201400008C; the Japan Initiative for Global Research Network on Infectious Diseases; Grants-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; Grants-in-Aid from the Ministry of Health, Labour and Welfare, Japan; grants from the Strategic Basic Research Program of the Japan Science and Technology Agency; and by the Advanced Research & Development Programs for Medical Innovation from the Japan Agency for Medical Research and Development (AMED). C.A.R. was supported by a University Research Fellowship from the Royal Society. The authors acknowledge a Netherlands Organisation for Scientific Research (NWO) VICI grant, European Union (EU) FP7 programs EMPERIE (223498) and ANTIGONE (278976); Human Frontier Science Program (HFSP) program grant P0050/2008; Wellcome 087982AIA; and NIH Director's Pioneer Award DP1-OD000490-01. D.F.B and D.J.S. acknowledge CamGrid, the University of Cambridge distributed computer system. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nmicrobiol.2016.5

Wiring of Photosystem II to Hydrogenase for Photoelectrochemical Water Splitting.

In natural photosynthesis, light is used for the production of chemical energy carriers to fuel biological activity. The re-engineering of natural photosynthetic pathways can provide inspiration for sustainable fuel production and insights for understanding the process itself. Here, we employ a semiartificial approach to study photobiological water splitting via a pathway unavailable to nature: the direct coupling of the water oxidation enzyme, photosystem II, to the H2 evolving enzyme, hydrogenase. Essential to this approach is the integration of the isolated enzymes into the artificial circuit of a photoelectrochemical cell. We therefore developed a tailor-made hierarchically structured indium-tin oxide electrode that gives rise to the excellent integration of both photosystem II and hydrogenase for performing the anodic and cathodic half-reactions, respectively. When connected together with the aid of an applied bias, the semiartificial cell demonstrated quantitative electron flow from photosystem II to the hydrogenase with the production of H2 and O2 being in the expected two-to-one ratio and a light-to-hydrogen conversion efficiency of 5.4% under low-intensity red-light irradiation. We thereby demonstrate efficient light-driven water splitting using a pathway inaccessible to biology and report on a widely applicable in vitro platform for the controlled coupling of enzymatic redox processes to meaningfully study photocatalytic reactions.This work was supported by the U.K. Engineering and Physical Sciences Research Council (EP/H00338X/2 to E.R. and EP/G037221/1, nanoDTC, to D.M.), the UK Biology and Biotechnological Sciences Research Council (BB/K002627/1 to A.W.R. and BB/K010220/1 to E.R.), a Marie Curie Intra-European Fellowship (PIEF-GA-2013-625034 to C.Y.L), a Marie Curie International Incoming Fellowship (PIIF-GA-2012-328085 RPSII to J.J.Z) and the CEA and the CNRS (to J.C.F.C.). A.W.R. holds a Wolfson Merit Award from the Royal Society.This is the final version of the article. It first appeared from ACS Publications via http://dx.doi.org/10.1021/jacs.5b0373

Sugary interfaces mitigate contact damage where stiff meets soft

The byssal threads of the fan shell Atrina pectinata are non-living functional materials intimately associated with living tissue, which provide an intriguing paradigm of bionic interface for robust load-bearing device. An interfacial load-bearing protein (A. pectinata foot protein-1, apfp-1) with L-3,4-dihydroxyphenylalanine (DOPA)-containing and mannose-binding domains has been characterized from Atrina's foot. apfp-1 was localized at the interface between stiff byssus and the soft tissue by immunochemical staining and confocal Raman imaging, implying that apfp-1 is an interfacial linker between the byssus and soft tissue, that is, the DOPA-containing domain interacts with itself and other byssal proteins via Fe3(+)-DOPA complexes, and the mannose-binding domain interacts with the soft tissue and cell membranes. Both DOPA-and sugar-mediated bindings are reversible and robust under wet conditions. This work shows the combination of DOPA and sugar chemistry at asymmetric interfaces is unprecedented and highly relevant to bionic interface design for tissue engineering and bionic devices